Proceedings of the 2012 Symposium on Agent Directed Simulation
Simulating plausible mechanisms for changing hepatic xenobiotic clearance patterns
Proceedings of the Winter Simulation Conference
Falsifying an Enzyme Induction Mechanism within a Validated, Multiscale Liver Model
International Journal of Agent Technologies and Systems
| Hi-index | 0.00 |
Results from simulation experiments falsified the hypothesis that a uniform distribution of simulated drug passing through an in silico liver (ISL) will produce a uniform extent of enzyme induction (EI). Wet-lab EI experiments, as formulated, are infeasible. The simulated EI is intended to have a hepatic counterpart. The ISL is synthetic, physiologically based, fine-grained, and multi-agent. It has been validated against in situ drug disposition data. We discuss methodological considerations regarding the phenomenal manifold, multi-level observation, and manipulation of synthetic models and their referents. Interestingly, a lower probability of metabolism caused higher EI and, counter-intuitively, more extraction. © 2008 Wiley Periodicals, Inc. Complexity, 2009 This article was submitted as an invited paper resulting from the “Understanding Complex Systems” conference held at the University of Illinois at Urbana-Champaign, May 2007.